Abstract
Huntingtin interacting protein 14 (HIP14, ZDHHC17) is a huntingtin (HTT) interacting protein with palmitoyl transferase activity. In order to interrogate the function of Hip14, we generated mice with disruption in their Hip14 gene. Hip14-/- mice displayed behavioral, biochemical and neuropathological defects that are reminiscent of Huntington disease (HD). Palmitoylation of other HIP14 substrates, but not Htt, was reduced in the Hip14-/- mice. Hip14 is dysfunctional in the presence of mutant htt in the YAC128 mouse model of HD, suggesting that altered palmitoylation mediated by HIP14 may contribute to HD.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acyltransferases / deficiency*
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Acyltransferases / genetics
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Acyltransferases / metabolism
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Animals
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Cell Death / genetics
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Corpus Striatum / metabolism
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Corpus Striatum / pathology
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Disease Models, Animal
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Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
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Enkephalins / metabolism
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Huntington Disease / etiology*
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Huntington Disease / genetics
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Huntington Disease / pathology
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Lipoylation / genetics*
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Mice
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Mice, Knockout
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Motor Activity / genetics
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Mutant Proteins / metabolism
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Nerve Tissue Proteins / deficiency*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurons / metabolism
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Neurons / pathology
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Serotonin Plasma Membrane Transport Proteins / genetics
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Serotonin Plasma Membrane Transport Proteins / metabolism
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Synapses / metabolism
Substances
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Dopamine and cAMP-Regulated Phosphoprotein 32
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Enkephalins
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Mutant Proteins
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Nerve Tissue Proteins
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Ppp1r1b protein, mouse
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Serotonin Plasma Membrane Transport Proteins
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Slc6a4 protein, mouse
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Acyltransferases
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Zdhhc17 protein, mouse